Rapid examination of the kinetic process of intramolecular lactamization of gabapentin using DSC–FTIR

• Published in: Thermochimica acta Vol. 486; no. 1; pp. 5 - 10
• Main Authors: Hsu, Cheng-Hung, Lin, Shan-Yang
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier B.V 20.03.2009; Elsevier
• Subjects: Anticonvulsants. Antiepileptics. Antiparkinson agents; Biological and medical sciences; DSC; DSC–FTIR; Gabapentin; Gabapentin-lactam; Intramolecular cyclization; Medical sciences; Neuropharmacology; Pharmacology. Drug treatments; Intramolecular cyclization; DSC–FTIR; TG; Gabapentin; DSC; Gabapentin-lactam; Differential scanning calorimetry; Fourier transformation; Lactam; Anticonvulsant; Infrared spectrometry; Solid state; Cyclization; Lactamization; DSC-FTIR; Aminoacid; Thermal analysis; Kinetics
• ISSN: 0040-6031; 1872-762X
• DOI: 10.1016/j.tca.2008.12.008

The thermal stability and thermodynamics of gabapentin (GBP) in the solid state were investigated by DSC and TG techniques, and FTIR microspectroscopy. The detailed intramolecular lactamization process of GBP to form gabapentin-lactam (GBP-L) was also determined by thermal FTIR microspectroscopy. GBP exhibited a DSC endothermic peak at 169 °C. The weight loss in TG curve of GBP suggested that the evaporation process of water liberated via intramolecular lactamization was simultaneously combined with the evaporation process of GBP-L having a DSC endothermic peak at 91 °C. A thermal FTIR microspectroscopy clearly evidenced the IR spectra at 3350 cm −1 for water liberated and at 1701 cm −1 for lactam structure formed due to the lactam formation of GBP. This study indicates that the activation energy for combined processes of intramolecular lactamization of GBP and evaporation of GBP-L was about 114.3 ± 23.3 kJ/mol, but for the evaporation of GBP-L alone was 76.2 ± 1.5 kJ/mol. A powerful simultaneous DSC–FTIR combined technique was easily used to quickly examine the detailed kinetic processes of intramolecular cyclization of GPB and evaporation of GBP-L in the solid state.